Schizophrenia is a severe and persistent psychiatric disorder that is characterized by significant impairments in cognitive function. Deficits in social cognition, or the ability to process, interpret, and regulate socio-emotional information, have been recently shown to be key rate-limiting factors to functional recovery from the illness, making them critical targets for treatment. Social-cognitive impairments reflect a presumed deficit in fronto-temporal brain function, and are unresponsive to extant pharmacologic interventions. Recently, a comprehensive cognitive rehabilitation approach known as Cognitive Enhancement Therapy (CET) has been shown to greatly improve social cognition in two NIH-supported clinical trials with schizophrenia patients. The beneficial effects of CET presumably reflect a change in underlying brain function, and when applied early in the course of illness CET may be able to capitalize on a neuroplasticity reserve to alter functional brain deficits. Indeed, we have recently shown that social-cognitive improvement in CET is associated with an enhanced structural integrity of fronto-temporal brain networks in the early course of the disorder. Beyond these initial observations, however, remarkably little is known about the neurobiologic effects of social-cognitive rehabilitation on brain function in schizophrenia. Research on the neurobiologic effects of psychosocial interventions is aligned with the NIMH priority goal of identifying neural mechanisms of psychiatric treatments, yet such studies have rarely been conducted in schizophrenia due to a lack of translational investigators trained in both intervention and neuroscience research. The purpose of this Mentored Patient-Oriented Career Development Award (K23) is to provide the applicant, a trained social worker and psychosocial interventionist, with the skills in neuroscience needed to bridge the fields of psychosocial treatment and neuroscience research in schizophrenia. The long-term goal of the applicant is to advance the treatment of schizophrenia through evaluating the effects of psychosocial interventions on the brain and developing novel psychosocial treatments to enhance brain function in the disorder. To accomplish this long-term goal, a multidisciplinary training plan has been developed to provide the applicant with complementary expertise in: (1) neuroanatomy and the neurobiology of schizophrenia; (2) social-cognitive and affective neuroscience, and (3) functional neuroimaging methods. The applicant will receive mentoring in a strong multidisciplinary environment from accomplished experts in the field of neuroscience, which will be combined with formal training and coursework designed to develop his expertise in translational neuroscience methods and approaches. A complementary research plan will conduct a cross-sectional, post-treatment outcomes study of the effects of CET on social-cognitive brain function in 32 patients in the early course of schizophrenia. This research plan will proceed by first characterizing the nature of deficits in brain function during social-cognitie processing in early course schizophrenia patients (N = 16) and matched healthy controls (N = 16) using a field standard functional neuroimaging paradigm of emotion perception, along with two novel social cognition paradigms of perspective-taking and emotion regulation. Subsequently, 16 patients in the early course of schizophrenia who have been treated with CET in a ongoing clinical service at the institution will be studied along with 16 carefully matched early course patients who have not been exposed to CET. Post-treatment functional neuroimaging data using the emotion perception, perspective-taking, and emotion regulation paradigms will be collected on both CET-exposed and CET non-exposed patients to examine the effects of the intervention on fronto-temporal brain function and connectivity. Together, these activities will support an R01 application to conduct a subsequent longitudinal randomized trial of CET effects on social-cognitive brain function, and provide the unique training and research experiences needed to enable the applicant to achieve his long-term goal of becoming an independent investigator of the effects psychosocial treatment on the brain in schizophrenia. Results from this area of investigation are expected to lead to new discoveries regarding brain plasticity in schizophrenia, identify the neural mechanisms that can support social-cognitive enhancement, and pave the way for refining existing and developing increasingly effective interventions for this highly disabling condition. PUBLIC HEALTH RELEVANCE: This project proposes to conduct a post-treatment investigation of the effects of social-cognitive rehabilitation on brain function in early course schizophrenia. The information gathered from the project is of significant public health relevance, in that it will begin to provide critical information on the neural mechanisms of social cognitive enhancement in the disorder and lead to the refinement of existing and development of novel interventions to address this highly disabling aspect of schizophrenia. In addition, this project is expected to begin to elucidate the capacity of the schizophrenia brain to respond to psychosocial intervention, which will mark an important advance in the understanding of brain plasticity and the pathophysiology of the disorder.